40 Hz Gamma Auditory Stimulation for Delirium Prevention in Critically Ill ICU Patients

Delirium is a common acute disturbance of attention and cognition among critically ill patients and is associated with prolonged mechanical ventilation, longer hospital stays, and increased mortality. This multicenter, quadruple-masked, randomized controlled trial will evaluate whether 40 Hz gamma auditory stimulation can help prevent delirium in mechanically ventilated adult ICU patients. A total of 142 participants aged 50 years or older who are expected to require mechanical ventilation for at least 48 hours will be randomly assigned in a 1:1 ratio to receive either 40 Hz gamma auditory stimulation or a silent audio track, in addition to standard ICU care. The assigned intervention will be delivered through identical earphones twice daily at 08:00 and 20:00, for 60 minutes per session, until extubation or Day 7 after randomization, whichever occurs first. The primary outcome is the number of delirium- and coma-free days during the first 7 days after randomization. Secondary outcomes include the incidence and duration of delirium during this period, duration of mechanical ventilation, length of ICU and hospital stay through Day 28, and 28-day all-cause mortality.

Inclusion Criteria: 1. Expected duration of mechanical ventilation of at least 48 hours. 2. Age 50 years or older, with no upper age limit. Exclusion Criteria: 1. Known moderate-to-severe neurocognitive or psychiatric disorders that would confound delirium assessment, such as dementia or schizophrenia. 2. Severe or worse hearing impairment, defined as Grade 3 or higher according to the World Health Organization classification of hearing impairment. 3. Previous treatment with antipsychotic medication. 4. Epilepsy or a history of epilepsy. 5. Moribund condition with an expected survival of no more than 24 hours. 6. Inability to wear earphones because of head trauma or surgery.